Subcortical microstructural impairment in amyotrophic lateral sclerosis: clinical correlates of neurite orientation dispersion and density imaging (NODDI) changes.

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving widespread network disruption beyond the motor cortex. Deep gray matter (DGM) nuclei, crucial for motor and cognitive integration, remain underexplored Methods: Diffusion-weighted MRI data were acquired from 23 ALS patients and 24 age- and sex-matched healthy controls. Orientation dispersion index (ODI), neurite density index (NDI), and free water fraction (FWF) were extracted from the bilateral thalamus, caudate, putamen, pallidum, hippocampus, and amygdala using the Destrieux atlas. Group comparisons and partial correlations were adjusted for age, sex, and disease duration. Results: No significant group differences in DGM volumes or NODDI-derived metrics survived correction for multiple comparisons. Within the ALS group, several nominal (uncorrected) associations were observed between DGM microstructural metrics and ALSFRS-R subscores. Reduced respiratory subscores were associated with higher ODI in the left thalamus (ρ = 0.57, Discussion: These findings suggest subtle and predominantly exploratory associations between DGM microstructural properties and clinical measures in ALS. NODDI derived metrics, particularly ODI and NDI, may provide sensitive indices of subcortical microstructural variation, warranting further investigation in larger cohorts.